ArticleJournal of leukocyte biology2012
BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction.
Article in Journal of leukocyte biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inhibitory Immune Checkpoint Molecule Expression in Clinical Sepsis Studies: A Systematic Review.Critical care medicine · 2020Pooled it
- Association between B and T lymphocyte attenuator/herpes virus entry mediator immunoregulatory axis and outcome prediction in a mixed critically ill population.Scientific reports · 2026Article
- BTLA-mediated regulation of neuroimmune responses enhances recovery after intracerebral hemorrhage.Journal of neuroinflammation · 2026Article
- Admission CD4Frontiers in cellular and infection microbiology · 2026Observational
- Lymphocyte function inhibition and exhaustion in sepsis: mechanisms and applications.Frontiers in immunology · 2026Review
- GM-CSF ameliorates inflammation from Pseudomonas aeruginosa in a juvenile mouse model of burn injury.Journal of leukocyte biology · 2025Article
- Article
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Immunophenotyping of septic shock patients with endotheliopathy: focus on monocyte subtypes and Immune regulatory molecules.Frontiers in immunology · 2025Article
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4Nature communications · 2024Article
- Herpes virus entry mediator signaling blockade produces mortality in neonatal sepsis through induced cardiac dysfunction.Frontiers in immunology · 2024Article
- The Calm after the Storm: Implications of Sepsis Immunoparalysis on Host Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy.Molecular cancer · 2023Review
- Pneumonia in the first week after polytrauma is associated with reduced blood levels of soluble herpes virus entry mediator.Frontiers in immunology · 2023Article
- Lymphocyte HVEM/BTLA co-expression after critical illness demonstrates severity indiscriminate upregulation, impacting critical illness-induced immunosuppression.Frontiers in medicine · 2023Article
- Immunomodulatory Properties of Immune Checkpoint Inhibitors-More than Boosting T-Cell Responses?Cancers · 2022Review
- Sustained elevation of soluble B- and T- lymphocyte attenuator predicts long-term mortality in patients with bacteremia and sepsis.PloS one · 2022Article
- Machine learning links different gene patterns of viral infection to immunosuppression and immune-related biomarkers in severe burns.Frontiers in immunology · 2022Article
- The Neonatal Innate Immune Response to Sepsis: Checkpoint Proteins as Novel Mediators of This Response and as Possible Therapeutic/Diagnostic Levers.Frontiers in immunology · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
A proper innate inflammatory response is essential for prevention of the systemic inflammation associated with sepsis. BTLA is an immune-regulatory receptor demonstrated to be expressed not only on adaptive immune populations and have potent inhibitory effects on CD4(+) T cells but is also expressed on innate cell populations (CD11c(+) and CD11b(+) cells) and has been shown to diminish pathogen clearance following bacterial and parasite infection. The role of BTLA in sepsis and the mechanisms by which BTLA alters pathogen clearance, however, have not been addressed clearly. Here, we show that following acute experimental sepsis induction in mice (CLP), the number of infiltrating BTLA- and HVEM (the ligand for BTLA)-expressing macrophages, inflammatory monocytes, mature and immature DCs, and neutrophils increased in the peritoneum compared with sham surgery, suggesting that a high level of HVEM:BTLA interactions occurs between these cells at the site of septic insult. Given this, we evaluated BTLA(-/-) mice, 24 h post-CLP, and observed a marked increase in the degree of activation on these cell populations, as well as a reduction in peritoneal bacterial burden and IL-10 induction, and most importantly, BTLA(-/-) mice exhibited a higher rate of survival and protection from organ injury when compared with WT mice. Such changes were not restricted to experimental mice, as circulating BTLA+ and HVEM+ monocytes and HVEM+ granulocytes were increased in septic ICU patients, supporting a role for BTLA and/or HVEM as potential, novel diagnostic markers of innate immune response/status and as therapeutic targets of sepsis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.